ORF10: Molecular Insights into the Contagious Nature of Pandemic Novel Coronavirus 2019-nCoV

Abstract

2019-novel coronavirus (nCoV), the virus causing Covid19 disease, is a highly contagious virus and has created a pandemic. In efforts to combat this virus, subunit vaccine designing using immunoinformatics tools was undertaken. During these studies, new hypotheses began to emerge, the prominent among these was that the newly acquired ORF10 protein may be the key protein responsible for its highly contagious nature. ORF10 is a hitherto unknown protein with no homology to any known protein in organisms present till date. Through immunoinformatics studies, it has been observed that among all ten 2019-nCoV proteins, ORF10 presents amongst the highest number of immunogenic, promiscuous CTL epitopes. These epitopes are part of a cluster with HTL epitopes, suggesting that there is a high degree of epitope conservation in ORF10. Conservation of protein sequence across organisms is not seen, and there is no known structural template on which to model and derive a

Characterization and structural prediction of the putative ORF10 protein in SARS-CoV-2

“…The first model was constructed using the QUARK web server whereas the second model was built using the I-TASSER web server. 36,37 Both models were different in terms of secondary structure and topology (Figure S2). The QMEAN global Z-scores (QUARK: −3.88 / I-TASSER: −2.63) for both models were lower, suggesting that the model produced in this study had higher global, and also local, quality (Figure S3).…”

“…These models were built using either the QUARK or I-TASSER web server. 36,37 Both models varied in placement of secondary structural elements and topology (Figure S2). The QMEAN global Z-scores for both models (QUARK: −3.88 / I-TASSER: −2.63) were lower, indicating the model produced in this study had higher global, and also local, quality scoring (Figure S3).…”

“…Global and local quality comparisons against two previously constructed models were also performed. 36,37…”

Computational Structural and Functional Analyses of ORF10 in Novel Coronavirus SARS-CoV-2 Variants to Understand Evolutionary Dynamics

“…Based on the newly available SARS-CoV-2 genome sequences, studies were undertaken to design potential vaccine candidates for multi-subunit vaccine. [2][3][4] On the way to ranking and designing these epitopes on the basis of relevant biological pathways and immunological parameters, viz., MHC class-I and class-II antigen processing and presentation pathways and immunogenicity, several useful insights into the genomic contribution to the deadly nature of this pathogen were found along the way. One of the insights led to the crucial leads on the role of an unknown gene 2 Evolutionary Bioinformatics sequence, called ORF10, in viral immunopathogenesis and evolution.…”

“…The aim of this study is to understand the structural and functional aspects of ORF10 gene-encoded protein in several variants, and its evolutionary dynamics on the basis of the predicted mutations in the key regions of its structure. A few studies specific to ORF10 have emerged only after the publication of these preprints from the author's lab at the time of first submission to ChemRxiv, preprint, March to April 2020, 2,3 and therefore, to the best of this author's knowledge, this study is the first one on analyzing the likely functional role of ORF10 based on its sequence conservation, structural analyses, and epitope compositions. Moreover, this study gains importance in view of the fact that this region is 100% conserved at nucleotide sequence level across geographical boundaries and major lineages, even in the WHO specified recent Variants of Concern (VOCs) and Variants of Interest (VOIs) including the dominant B.1.1.529, B.1.617, B.1.1.7, P.1, and B.1.351 lineages, and therefore, needs attention as to its likely functional role in evolution.…”